This invention relates to a commercially feasible, efficient process for the preparation of a high quality substantially pure or 100% pure trans-.DELTA..sup.9 -isoambrettolide for use in the perfume industry.
The macrocyclic compounds, i.e., trans-.DELTA..sup.9 -isoambrettolide, prepared by the process of the present invention, are musk odorants and as such are highly desirable. The odor of musk is perhaps the most universally appreciated fragrance and is usually thought of as the animal note in perfumes. A number of naturally occurring species, both of animal and vegetable origin, possess musk odors; however, only three animal sources have achieved any commercial importance. It is because of the high demand and short supply of these naturally occurring musk odorants that numerous attempts have been made since the 1920's to synthesize compounds which would duplicate these desirable odors. Isoambrettolide has the formula: ##STR1##
Ambrettolide has the formula: ##STR2##
Ambrettolide itself naturally occurs in musk ambrette seed oil and is a valuable perfume base because of its desirable odor. Ruzicka and Stoll [Helv.Chem.Acta., 17, 1609(1928)] show a method for preparing macrocyclic lactones involving the oxidation of macrocyclic ketones with Caro's acid (persulfuric acid) to the corresponding lactones. Ambrettolide is said to be prepared by this method. U.S. Pat. No. 2,417,151 discloses a process for the preparation of ambrettolide involving intramolecular esterification. In this process sodium 6,16-dihydroxypalmitate is condensed with 1-chloropropanediol-2,3 to form the glycerol monoester which is treated with sodium acid sulfate to produce a mixture of unsaturated isomeric glycerol mono-esters. This mixture is then distilled and worked up to yield a mixture of unsaturated isomeric large-ringed cyclic lactones including ambrettolide which can be separated out, if desired.
Trans-.DELTA..sup.9 -isoambrettolide has preferably been produced from aleuritic acid by means of a much more complicated process; that is, by first forming the mono-acetate; then acetylating this mono-acetate; then mono-brominating the acylated aleuritic acid diacetate to form brombengal acid; dehydrohalogenating the brombengal acid using zinc to form bengalene acid; then, using ethylene glycol, trans-esterifying bengalene acid in the presence of a potassium glycolate catalyst whereby a poly-bengalene acid is formed, which is then trans-esterified to form trans-.DELTA..sup.9 -isoambrettolide; but not in pure form. This reaction sequence is set forth schematically as follows: ##STR3##
Sabnis, et al., J.Chem.Soc. 1963, 2477-8, discloses a complicated synthesis of ambrettolide from aleuritic acid according to the following reaction scheme: ##STR4##
Another process for producing ambrettolide or iso-ambrettolide is set forth in U.S. Pat. No. 3,681,395, issued on Aug. 1, 1972 and this process discloses the following steps:
1. epoxidizing 1,9-cyclohexadecadiene of the structure ##STR5## to form a diepoxidized cyclohexadecane of the structure ##STR6## and
2. reducing said diepoxidized cyclohexadecane to form a mixture of cyclohexadecadiols of the structures ##STR7## and
3. oxidizing said cyclohexadecadiols to form the corresponding hydroxy ketones of the structures ##STR8## and
4. treating said hydroxy ketones with a peracid in the presence of a boron trifluoride etherate catalyst to form a mixture of hydroxy cyclohexadecanolides of the structures ##STR9## and
5. dehydrating said hydroxy cyclohexadecanolides to obtain the desired mixture of ambrettolide and isomers thereof of the general structure ##STR10## wherein x is 5, 6, 7 and 8 and y is 8, 7, 6 and 5, respectively and x plus y equals 13; said mixture can be separated by conventional means, if desired, into the various isomers, e.g., when x is 5 and y is 8 the lacetone is ambrettolide and when x is 7 and y is 6 the lactone is iso-ambrettolide.
However, nothing exists in the prior art showing a three step preparation from aleuritic acid easily to form substantially pure trans-.DELTA..sup.9 -isoambrettolide.
Eastwood, et al., Tetrahedron Letters, No. 60, 5223-24, 1970, discloses a technique for converting 2-dimethylamino-1,3-dioxolane into alkenes according to the following reaction sequence: ##STR11##
There is nothing in the Eastwood, et al. article which suggests that this reaction can be applied in the complicated process for producing trans-.DELTA..sup.9 -isoambrettolide.
By the same token, Crank and Eastwood, Australian Journal of Chemistry, 1964, 17, 1392-8, discloses the introduction of a double bond in place of a diol moiety by use of a dioxolane intermediate according to the following reaction sequence: ##STR12##
Again, the disclosure of such a reaction sequence does not suggest the use of the reaction in the production of trans-.DELTA..sup.9 -isoambrettolide.